Everything that needs to be said has already been said. But since no one was listening, everything must be said again. @briansfeldman

Mar 14, 2014

A Hundred Thousand Hourglasses

The Secret Life of a Secret Cell

Stained Purkinje Cell from a Human Cerebellum (Creative Commons)

If a mid-19th century European—a Prussian, let’s say—wanted to contact famed Czech histologist Jan Evangelista Purkinje, he only needed to address his envelope with two words: Purkinje, Europe; so large was Purkinje’s renown, that his dwelling was an entire continent. It’s therefore fitting that this man’s address—sprawling, yet laconic—parallels one of his most famous biological discoveries: Purkinje cells.

Born in 1787 to a housewife and a German priest, Purkinje was raised in Bohemia (now Czech Republic) and graduated in 1818 with a degree in medicine. He was soon appointed as a Professor of Physiology at Prague’s Charles University where he taught and conducted research on human anatomy. In addition to discovering Purkinje images (reflections of objects from structures of the eye) and the Purkinje shift (the change in the intensity of red and blue colors as light intensity ebbs at nightfall) he also proposed the scientific term for plasma, the colorless fluid part of blood, lymph, or milk, in which corpuscles or fat globules are suspended. Today, his name also adorns a university in Ústí nad Labem, Czech Republic; a crater on the Moon; and a small asteroid (#3701), but he lives on—commemorated best, I like to think—as an elegant cerebellar cell.

Discovered in 1837 by accident, his now-eponymous neurons—specialized brain cells that transmit nerve impulses—are, like his physical address, vast — especially by molecular standards. Their sprawling ninety-micron-long cell bodies surpass the length of a wispy arm hair and their structure is more elegant than that of a tapered hirsute tube. The cells’ hallmark, their dendrites—branched extensions which receive nerve impulses—resemble well-painted latticework; razor-edged angles jut out where bundles of Purkinje cells crisscross over one another and jagged forking structures curlicue squarely, sculpting dramatic looms of polygon-like geometry.

Using an electron scanning microscope and fluorescent cell tracing—a microinjection of colorful dye that distinguishes a cell’s disparate components—a rudimentary blueprint emerges: the cell body—the soma—fans out and joins the tree-like dendrites at one end, and at the other, the axon—nerve cells’ threadlike part along which impulses are conducted—moves into view. In artistic terms, the Purkinje cell resembles one of Picasso’s cubist portraits, a sequenced collage of simple geometric shapes, interlocking planes; we’re not dealing with a Pollack or a piece of po-mo abstract expressionism here.

Their orderliness, you see, makes sense.

Unlike other neurons whose cells are tangled, messy like the creepers of a dense patch of brambles, Purkinje cells’ sprawling spick-and-span structures inform their function. The neurons reside in the cerebellum, more specifically the cerebellar cortex, a half-pound Jell-O-like part of the brain that coordinates and regulates muscle activity. The cerebellum, as a cheeky neuroscientist professor of mine once put it, is a correction machine. Whenever you move your hand to clutch a cup of coffee or tap your toes rhythmically as you wait in line with anticipation, the cerebellum continuously monitors these movements, ensuring that you don’t miss the mug’s handle or that you don’t clomp your entire foot all Goofy-like. The cerebellum is perpetually—but not slavishly—comparing your mental thoughts (imagined movement) with your actual movement to match the two as closely as possible.

Given the amount of energy involved in motor movement, the Purkinje cells’ consortium of fan-like dendrites collects all of the nerve impulses responsible for physical action. One lone Purkinje cell’s dendrites, for instance, acquire converging inputs—neuronal messages—from over a million other cells, mostly those called mossy or climbing fibers. The former originate in the brain stem or spinal cord by means of granule cells—one of the small neurons of the cerebellar cortex—and branch out to contact the thirty-million Purkinje cells spread out like an Ancient Japanese hand fan. Unlike the mossy fibers, the climbing fibers originate in the medulla oblongata—the continuation of the spinal cord within the skull, forming the lowest part of the brainstem—and connect one-on-one with Purkinje cells to deliver certain neuronal messages.

Think of it like this: the climbing fibers are like a speedy, but less-commonly-used bike courier who delivers messages emblazoned with ‘URGENT’ as quickly as possible, whereas the mossy fibers are like a slogging USPS mailman pushing kitschy ads and spam mail through your front door’s mail slot. Interestingly, nerve impulses that require memory—muscle memory in particular—use the climbing fibers to ensure that the message is transmitted clearly and expertly. Actions that have become habitual and thus require less cellular energy (something as basic as walking or as complex as giving a handshake), opt for the USPS-mailman approach.

Granted that fibers and excitatory cells—those which create a symphony of near-continuous firings and chemical signals urging movement—provide input to Purkinje cells, the Purkinje cells themselves are inhibitory; they selectively limit and sort out all of the nerve impulses. They are laconic modulators. They are like a hundred thousand hourglasses sieving not the all-too-common ‘sands of time’ but the chattering electrical impulses which encode movement.

If you’re a cranky pessimist, the Purkinje cells might seem like fascists or other autocrats, but if you’re an easygoing optimist, they’re like a good set of parents: strict, but always looking out for your best interests. That is, since there are one-hundred-billion fibers connecting to thirty-million Purkinje cells’ arbor-like dendrites, one lone Purkinje cell integrates, controls, and then processes signals from an astounding 3,000 nerve fibers.

They are thus like talented black-tuxedo-wearing composers silencing orchestral ‘noise’ and bringing out each member’s inner Mozart or Beethoven: virtuous, euphonious, lilting. They are like a bunch of robust dams selectively blocking a tidal wave of chatty nerve impulses. They are Ockham’s Razor at its finest, slicing and dicing and funneling and synthesizing only what the mind deems most significant.

So it is impressive that in our brains—that in the very seats of consciousness—our thinking machines abide by the reverent rule of parsimony. I’m apt to avoid the naturalistic fallacy, and have my qualms with evolutionary psychology, but with cells designed so simply—hewing so closely to Aquinas’ aphorism “If a thing can be done adequately by means of one, it is superfluous to do it by means of several”—I cannot help but wonder if in a three-pound assemblage of purple-veined tissue might we read, quite literally, this maxim: Everything should be kept as simple as possible, but no simpler.

The Purkinje cells are structured magnificently, but only in a manner that ensures economical functioning; one missing diamond-shaped space in the neuronal latticework, one too-many polygonal Purkinje cells, and the nerve impulse’s entire message would be lost, translated less accurately. And the Purkinje cells aren’t just a human adaptation. They’re found in the brains of birds and fish and reptiles and the earliest vertebrates.

It therefore seems that the Purkinje cell has used its energy capital efficiently, and has adapted to the fact that our bodies—and that our Earth—contain a limited amount of energy; what I find most impressive about the Purkinje cells is that in a world as complex as the one in which we live, all life—not just us—has adapted to the earthly challenge of survival by evolving a cell that takes a flurry of complex information and distills it into a simple, clear message just so that we can move ourselves either forward and backward or side-to-side or from point A to point B. And then do it all again.

Without these cells, we would then, as obvious as it seems, be highly uncoordinated; we would be stamping around like a big, thumping, thudding, stamping mess. We would drop our coffee mugs completely. We would catch baseballs shoddily. Hugging would be unwieldy. Unverrict-Lundorg disease, a neurodegenerative disorder, illustrates the consequences of damaged Purkinje cells; it brings adolescents to the brink of overpowering epileptic fits.

With the decrease in motor coordination, sudden, violent, irregular movements of limbs—caused by involuntary contraction of muscles—turn the body into a too-rigid stick figure; ataxic tremors, a stiff gait, and a diminished ability to determine space render the body’s fluidity as inelastic, stiff, taut. The disease is rare—only Finland reports an incidence, four in one hundred thousand—but its existence still underscores the importance of these often overlooked ninety-micron-long cells; let us not forget that in our bodies, in our brains, in our cerebellums, in our cerebellar cortexes, nestled between layers of sinews and other types of proteins and chemicals whose names still remain undiscovered and unnamed, there resides an address sprawling yet laconic: Purkinje cells.